Effect of dalcetrapib, a CETP modulator, on non-cholesterol sterol markers of cholesterol homeostasis in healthy subjects

Atherosclerosis

Volumn 219, Issue 2, 2011, Pages 761-767

  Niesor, Eric J ^a   Chaput, Evelyne ^a   Staempfli, Andreas ^a   Blum, Denise ^a   Derks, Michael ^a   Kallend, David ^a  

^a F HOFFMANN LA ROCHE LTD   (Switzerland)

Author keywords

Sitosterol; Campesterol; Cholestanol; Cholesterol absorption; Cholesterol homeostasis; Cholesterol synthesis; Cholesteryl ester transfer protein (CETP); Dalcetrapib; Desmosterol; Ezetimibe; Hamster; High density lipoprotein (HDL); Lathosterol; Non cholesterol sterols; Phytosterols

Indexed keywords

ABC TRANSPORTER A1; CAMPESTEROL; CHOLESTANOL; DALCETRAPIB; DESMOSTEROL; EZETIMIBE; HIGH DENSITY LIPOPROTEIN CHOLESTEROL; LATHOSTEROL; LOW DENSITY LIPOPROTEIN CHOLESTEROL; SITOSTEROL; TORCETRAPIB; TRIACYLGLYCEROL; VERY LOW DENSITY LIPOPROTEIN CHOLESTEROL;

ADULT; ARTICLE; CHOLESTEROL BLOOD LEVEL; CHOLESTEROL METABOLISM; CHOLESTEROL SYNTHESIS; CONTROLLED STUDY; CROSSOVER PROCEDURE; DRUG EFFECT; HAMSTER; HUMAN; HUMAN EXPERIMENT; LIPID ABSORPTION; MALE; NONHUMAN; NORMAL HUMAN; OPEN STUDY; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL;

ANIMALS; ANTICHOLESTEREMIC AGENTS; AZETIDINES; BIOLOGICAL MARKERS; CHOLESTANOL; CHOLESTEROL; CHOLESTEROL ESTER TRANSFER PROTEINS; CHOLESTEROL, HDL; CRICETINAE; CROSS-OVER STUDIES; DESMOSTEROL; HOMEOSTASIS; HUMANS; INTESTINAL ABSORPTION; LIPID METABOLISM; MALE; MESOCRICETUS; MODELS, ANIMAL; PHYTOSTEROLS; QUINOLINES; SITOSTEROLS; SULFHYDRYL COMPOUNDS; SWITZERLAND;

EID: 82955184596     PISSN: 00219150     EISSN: 18791484     Source Type: Journal    
DOI: 10.1016/j.atherosclerosis.2011.09.017     Document Type: Article

References (30)

1. Miettinen T.A., Tilvis R.S., Kesaniemi Y.A. Serum plant sterols and cholesterol precursors reflect cholesterol absorption and synthesis in volunteers of a randomly selected male population. Am J Epidemiol 1990, 131:20-31.
2. Matthan N.R., Resteghini N., Robertson M., et al. Cholesterol absorption and synthesis markers in individuals with and without a CHD event during pravastatin therapy: insights from the PROSPER trial. J Lipid Res 2010, 51:202-209.
3. Miettinen T.A., Gylling H. Synthesis and absorption markers of cholesterol in serum and lipoproteins during a large dose of statin treatment. Eur J Clin Invest 2003, 33:976-982.
4. Assmann G., Kannenberg F., Ramey D.R., et al. Effects of ezetimibe, simvastatin, atorvastatin, and ezetimibe-statin therapies on non-cholesterol sterols in patients with primary hypercholesterolemia. Curr Med Res Opin 2008, 24:249-259.
5. Sudhop T., Reber M., Tribble D., et al. Changes in cholesterol absorption and cholesterol synthesis caused by ezetimibe and/or simvastatin in men. J Lipid Res 2009, 50:2117-2123.
6. Miettinen T.A., Kesaniemi Y.A. Cholesterol absorption: regulation of cholesterol synthesis and elimination and within-population variations of serum cholesterol levels. Am J Clin Nutr 1989, 49:629-635.
7. Wilund K.R., Feeney L.A., Tomayko E.J., et al. Effects of endurance exercise training on markers of cholesterol absorption and synthesis. Physiol Res 2009, 58:545-552.
8. Nunes V.S., Leanca C.C., Panzoldo N.B., et al. HDL-C concentration is related to markers of absorption and of cholesterol synthesis: study in subjects with low vs. high HDL-C. Clin Chim Acta 2011, 412:176-180.
9. Lupattelli G., Pirro M., Siepi D., et al. Non-cholesterol sterols in different forms of primary hyperlipidemia. Nutr Metab Cardiovasc Dis 2010, August. [Epub ahead of print].
10. Barter P.J., Kastelein J.J. Targeting cholesteryl ester transfer protein for the prevention and management of cardiovascular disease. J Am Coll Cardiol 2006, 47:492-499.
11. Clerc R.G., Stauffer A., Weibel F., et al. Mechanisms underlying off-target effects of the cholesteryl ester transfer protein inhibitor torcetrapib involve L-type calcium channels. J Hypertens 2010, 28:1676-1686.
12. Forrest M.J., Bloomfield D., Briscoe R.J., et al. Torcetrapib-induced blood pressure elevation is independent of CETP inhibition and is accompanied by increased circulating levels of aldosterone. Br J Pharmacol 2008, 154:1465-1473.
13. Stroes E.S., Kastelein J.J., Benardeau A., et al. Dalcetrapib: no off-target toxicity on blood pressure or on genes related to the renin-angiotensin-aldosterone system in rats. Br J Pharmacol 2009, 158:1763-1770.
14. Collet X., Tall A.R., Serajuddin H., et al. Remodeling of HDL by CETP in vivo and by CETP and hepatic lipase in vitro results in enhanced uptake of HDL CE by cells expressing scavenger receptor B-I. J Lipid Res 1999, 40:1185-1193.
15. Gauthier A., Lau P., Zha X., Milne R., McPherson R. Cholesteryl ester transfer protein directly mediates selective uptake of high density lipoprotein cholesteryl esters by the liver. Arterioscler Thromb Vasc Biol 2005, 25:2177-2184.
16. Niesor E.J., Magg C., Ogawa N., et al. Modulating cholesteryl ester transfer protein activity maintains efficient pre-beta-HDL formation and increases reverse cholesterol transport. J Lipid Res 2010, 51:3443-3454.
17. Field F.J., Born E., Mathur S.N. LXR/RXR ligand activation enhances basolateral efflux of beta-sitosterol in CaCo-2 cells. J Lipid Res 2004, 45:905-913.
18. Derks M., Abt M., Phelan M. Lack of clinically relevant drug-drug interactions when dalcetrapib is co-administered with ezetimibe. Br J Clin Pharmacol 2010, 70:825-833.
19. Lütjohann D., Björkhem I., Beil U.F., Von Bergmann K. Sterol absorption and sterol balance in phytosterolemia evaluated by deuterium-labeled sterols: effect of sitostanol treatment. J Lipid Res 1995, 36:1763-1773.
20. Evans G.F., Bensch W.R., Apelgren L.D., et al. Inhibition of cholesteryl ester transfer protein in normocholesterolemic and hypercholesterolemic hamsters: effects on HDL subspecies, quantity, and apolipoprotein distribution. J Lipid Res 1994, 35:1634-1645.
21. Brousseau M.E., Diffenderfer M.R., Millar J.S., et al. Effects of cholesteryl ester transfer protein inhibition on HDL subspecies, apolipoprotein A-I metabolism, and fecal sterol excretion. Arterioscler Thromb Vasc Biol 2005, 25:1057-1064.
22. Field F.J., Watt K., Mathur S.N. Origins of intestinal ABCA1-mediated HDL-cholesterol. J Lipid Res 2008, 49:2605-2619.
23. Drobnik W., Lindenthal B., Lieser B., et al. ATP-binding cassette transporter A1 (ABCA1) affects total body sterol metabolism. Gastroenterology 2001, 120:1203-1211.
24. Matthan N.R., Pencina M., Larocque J.M., et al. Alterations in cholesterol absorption/synthesis markers characterize Framingham offspring study participants with CHD. J Lipid Res 2009, 50:1927-1935.
25. Silbernagel G., Fauler G., Renner W., et al. The relationships of cholesterol metabolism and plasma plant sterols with the severity of coronary artery disease. J Lipid Res 2009, 50:334-341.
26. Weingartner O., Lutjohann D., Bohm M., Laufs U. Relationship between cholesterol synthesis and intestinal absorption is associated with cardiovascular risk. Atherosclerosis 2010, 210:362-365.
27. Teupser D., Baber R., Ceglarek U., et al. Genetic regulation of serum phytosterol levels and risk of coronary artery disease. Circ Cardiovasc Genet 2010, 3:331-339.
28. Pinedo S., Vissers M.N., Von Bergmann K., et al. Plasma levels of plant sterols and the risk of coronary artery disease: the prospective EPIC-Norfolk Population Study. J Lipid Res 2007, 48:139-144.
29. Escurriol V., Cofán M., Moreno-Iribas C., et al. Phytosterol plasma concentrations and coronary heart disease in the prospective Spanish EPIC cohort. J Lipid Res 2010, 51:618-624.
30. Tilvis R.S., Miettinen T.A. Serum plant sterols and their relation to cholesterol absorption. Am J Clin Nutr 1986, 43:92-97.